The separation is the critical technique involved in the biochemical detecting. Separation techniques, such as the physical filtration, crystallization and distillation have been widely applied to separate cells or fragments of cells from aqueous solutions or suspensions However, these techniques have become more and more insufficient as the quantity of the material to be purified becomes smaller and the compactness of the detecting device needs to be realized.
The magnetic separation is a well-known technique in the biotechnology, and the magnetic beads have recently been used to help the manipulating and transporting of bio-molecules. It is possible to satisfy the above demands by adopting the magnetic-bead separation technique for the flexibility in controlling.
The working principle of the magnetic-beads separation technique is that the target cells and bio-molecules would be separated form the sample liquid and then transmitted to a specific position by the magnetic-beads via the sampled cells or bio-molecules adsorbed on the magnetic beads. Many efforts have been done in this technique. Not only the microfluidic channels, the micromechatronics processing and the electromagnet, which is used for attracting and adsorbing the magnetic beads, but also the shapes, the sizes and the fabrications of the electromagnets have been developed already. Furthermore, the applications for the biochemical detectings including the relevant biochemical reactions, the detecting processes and the signal measurements also have been mentioned.
Please refer to FIGS. 1, 2 and 3, wherein FIG. 1 is a schematic view illustrating the structure of a first conventional magnetic-bead biochemical detecting device 1′, FIG. 2 is a cross-sectional view according to the line A–A′ in FIG. 1, and FIG. 3 illustrates the structure of the electromagnet of the detecting device 1′ in FIG. 1. As shown in FIGS. 1 and 2, the detecting device 1′ is mainly formed by a substrate 18′, an electromagnet 13′ located thereon having an embedded serpentine conductor structure 23′, the magnetic layer 24′ of a permalloy and a microfluidic channel 12′ with a gap layer 16′ therebetween. Furthermore, bonding pods 17′ are configured to make an electric connection to the electrically driving system (not shown), and a fluid inlet 11′ and a fluid outlet 14′ are configured on a lid 15′, which may be made of glasses. The embedded serpentine conductor structure 23′ of the electromagnet 13′ has plural conducting wires 34′, one of which is further enlarged in FIG. 3.
Accordingly, the electromagnet 13′ is an additional arrangement to the microfluidic channel 12′, wherein the electromagnet 13′ and the microfluidic channel 12′ are independently fabricated on different chips and then joined together. The electromagnet 13′ itself could not drive the fluid to flow, and an additional fluid driver is hence needed. The fluid driver makes the detecting process more complicated and a less precise detection result would be resulted therefrom. Therefore, such a detecting device 1′ is used only for magnetic-beads detecting and lacks the applicability and the benefit in integration.
Besides, since the detecting device 1′ mentioned above is configured to be operated through the continuous flow, it has a lot of drawbacks, such as a large amount of the reagent is necessary, the samples mixing is insufficient, it is much difficult to drive the fluids, the problem of time-consuming is serious and the detecting result is not precise enough.
Please refer to FIG. 4 illustrating the structure of a second detecting device according to the prior art. The detecting device 4′ disclosed in the U.S. Pat. No. 6,116,863 includes plural electromagnetic drivers 41′ disposed on a first substrate 40′ and a spiral coil 42′ encapsulated by an overlapping magnetically permeable core 43′. Furthermore, a second substrate 50′ is also used in the detecting device 4′ to form a diaphragm 48′and a boss 46′, and a magnetic permeable material 45′ may be electroplated on the diaphragm 48′. Additionally, a third substrate 60′ is applied to form valve seats 47′ and a microfluidic channel 49′. Such a detecting device 4′ is further improved to apply in the magnetic controlling and detecting.
Please refer to FIG. 5, which schematically illustrates the electromagnetic driver 41′ in FIG. 4 in greater detail. The spiral coil 42′ includes an outer lead wire 42a′ and an inner lead wire 42b′. An insulator layer (not shown) interposed between the out lead wire 42a′ and the inner lead wire 42b′ generally insulates the spiral coil 42′ from the core 43′. Furthermore, the electromagnetic driver 41′ has a central via 51′ and a plurality of peripheral vias 52′.
Please refer to FIG. 6 illustrating a magnetic particle separator 6′ according to the prior art. The magnetic particle separator 6′ disclosed by the U.S. Pat. No. 5,655,665 includes a microfluidic channel 63′ and two integrated inductive components 61′ respectively located on one side of the microfluidic channel 63′. The integrated inductive components 61′ are configured to attract and adsorb the magnetic beads thereon. The ends 62′ of the magnetic cores of the inductive components 61′ are disposed adjacent to the microfluidic channel 63′ and the conductors of the inductive components 61′ are electrically coupled to bonding pads 64′ which, in operation, receive a DC voltage. Please refer to FIG. 7, which is an enlarged schematic diagram illustrating the structure of the integrated inductive component 61′ in FIG. 6. Accordingly, the integrated inductive component 61′ is realized by wrapping the magnetic core 71′ around a planar meander conducting line 72′. In such a designed magnetic particle separator, however, the continuous flow is utilized for the magnetic-beads operating and controlling, and an additional driver (not shown) for driving the fluid to flow is still needed.
The above descriptions demonstrate the technical principles and applications of the magnetic-beads detecting technique. Moreover, the technique relative to electrowetting will be further explained as follows.
The electrowetting relates to the phenomenon that the hydrophobic-hydrophilic conversion of the droplets is occurred between the droplet and the contact surface, and the conversion would be affected by an applied electric potential. The droplet is further being driven to move by the surface tension imbalance thereof. Methods of adopting the phenomenon for driving the fluid are almost completely developed. Accordingly, several fundamental operations for droplets, in particular, the fluid mixing based on the droplets, could be operated by a single arrangement. The droplets are able to move in a plane of two-dimension through a specific arrangement of the electrode, which improves the degree of freedom and the practicability of the electrowetting actuated device.
Please refer to FIG. 8, which illustrates the conventional electrowetting actuated device. The electrowetting actuated device 8′ is mainly configured by an electrode 84′ on a substrate 82′, and a gap 83′ is formed therebewteen. Moreover, the electrowetting actuated device 8′ has a lid 81′ covered thereon for protection. It is worthy to be mentioned that the electrode 84′ in the electrowetting actuated device 8′ is just designed to drive the droplets 85′ through the disclosed shape of the electrode 84′, which has limited the practicability of the electrowetting actuated device 8′.
Therefore, it is predictable that the electrowetting actuated device will have an additional function by changing the shapes and arrangements of the electrodes and its practicability will be improved accordingly, while the droplets are driven to move.
Please refer to FIG. 9 illustrating the electrode set, which is disclosed by the prior art, U.S. Pat. No. 6,565,727. The electrode set 9′ includes a plurality of electrodes 91′ and a circular arrangement of sectorial electrodes 92′. Such an electrode set enables the fluid to move in circular.
As a result, it is apparent that a specific function of the electrowetting actuated device would be achieved by a specific arrangement or a specific shape of the designed electrodes. However, an integrated function of the magnetic-beads detecting technique with the electrowetting driving technique is not realized nowadays.
In order to overcome the drawbacks in the prior art, it is feasible to replace the continuous flows by the droplets in the magnetic-beads detecting technique. In other words, it is a more potential application of combining the electrowetting device with the magnetic-beads detecting device through a novel arrangement of the electrode.
Based on the above, it is possible to provide a more complete, convenient and practical detecting system by combining the electrowetting actuated device with the magnetic-beads detecting device, in particular, by integrating the electromagnet of the detecting device with the electrode of the electrowetting actuated device. The integrated detecting device provided by the present invention is fabricated through a simpler process, and can improve the efficiency of the conventional magnetic-beads biochemical detecting system.